This invention relates to the generation in convenient form of objective data from tablet presses, which information is particularly useful in the development and control of pharmaceutical granulations from the standpoint of tabletting characteristics, and more particularly relates to measurement and processing of the compression and ejection forces developed in tabletting machines and the use of this information in the development and optimization of tabletted pharmaceutical granulations. The tabletting characteristics herein contemplated comprise compressibility, lubrication as it pertains to die wall-adhesion, tendency to laminate or cap, flowability of the material, and tendency to stick or adhere to the punch surfaces following tablet formation.
The value of instrumenting tablet presses for investigating the fundamental aspects of tabletting has been clearly recognized for some time. The reader is referred, for example to Higuchi et al "The Physics of Tablet Compression III; Design and Construction of an Instrumented Tabletting Machine", Journal American Pharmaceutical Association, Sci. Ed. 43, 322-348, 1954; and Knoechel, et al, "Instrumented Rotary Tablet Machines I", Journal of Pharmaceutical Sciences, Vol. 56, No. 1, January 1967.
This technology has been refined and commercialized primarily as a production control tool to automatically adjust tablet weight (for example, U.S. Pat. No. 3,255,716, "Measurement of Forces Within a Tabletting Machine"; U.S. Pat. No. 3,507,388, "Apparatus for Sorting Tablets"; and U.S. Pat. No. 3,734,663, "Arming Control for Servo-Adjusted Tablet Compression Machines"). Up to now, there has been little refinement of the basic technology to provide a pharmaceutical development tool which is accurate, fast and simple to use.
Previous technology in tabletting instrumentation as a development tool has the drawback of being awkward and difficult to use, in that it required, in addition to a sensing device (e.g. a strain gauge arrangement) being installed on a tablet press, that the raw analog signals from that sensor be either displayed on an oscilloscope or recorded on an oscillographic recorder. Such is demonstrated, for example, in British Patent Specification No. 1,216,397, "Improvements In or Relating to Tablet Forming Machines". It was then necessary to measure the peaks of the obtained traces (usually manually) and convert the values to force values. These values were then tabulated and the average and standard deviation were calculated. One could in this way, with appropriate equipment selectivity and sensitivity, measure and process the ejection force information. Attempts along these lines hve also proven to be, overall, a very time-consuming and tedious process. Reference here to equipment selectivity and sensitivity concerns the additional problem of obtaining a clear "signature" or pickup of the ejection forces, i.e. identifying the ejection peaks from all other portions of the analog signal, which signal may very well have significant noise or interference riding thereon. The substantial problem of automating the identification and processing of the ejection force peaks of the analog waveform is put squarely in prospective when one considers that ejection information is to be obtained from an analog waveform in which the compression peaks have a magnitude in the vicinity of twenty-five to fifty times the magnitude of the ejection force.
Additionally, generally speaking, commercial efforts in this technology area have been limited to the objective of obtaining a running average of the peak compression forces alone, whereas it is deemed most desirable to provide for the measurement and processing of the compression force and also the ejection force for each tabletting event.
In the pursuit of the highly desirable concept of utilizing compression and ejection force information, individualized to each tabletting event, as a development tool in particular, the benefits of providing this information in digital form, which is easy to interpret, easy to relate and to establish limits relative thereof, are quickly recognized.
More particularly, compression and ejection force information should be provided in a form that may be readily employed to generate for example compression and ejection profiles, which in turn enable the formulator to easily and quickly derive information concerning relative compressibility, relative flow of the material, relative lubricity, and other tabletting characteristics. It is to be noted that certain of these tabletting characteristics are interrelated, as for example, the situation wherein the addition of a lubricant to a formulation to effect proper tabletting will have an effect on the compressibility of that formulation. Sufficient information is, by this invention, now made available to the formulator in a convenient form to enable quick determination of the proper amount of lubrication additive to achieve a "best of both worlds" solution.
It is moreover, of very sustantial benefit to the formulator to have available information regarding the average and standard deviation of a number of successive tablets as to both compression and ejection aspects to enable optimization of a particular formulation in the development phase from a tabletting characteristics standpoint.
It is, in addition, of considerable concern to the formulator to be able to evaluate new formulations (and also perhaps competitive formulations) and to optimize such formulations with regard to tabletting characteristics with only a minimum amount of material available. All too often, a tabletted formulation has to be finalized and optimized at a very early stage in the total picture leading to the marketing of an acceptable tabletted drug product. Normally, initial batches are employed in very expensive clinical trials, the data from which is to be used for example in new drug application filings and the like to gain Governmental approval of the product. Demands are thus made on formulators to come up with a final formula before substantial quantities of the product are available to work with.